Updates to DUX4 region on subtelomeric chromosome 4q

Sequence improvements and increased variant representation in the human genome reference assembly are priorities for the GRC. This blog post describes two updates in the recent GRCh38.p7 patch release affecting the DUX4 region located at the chromosome 4q sub-telomere: (1) a FIX patch correcting the chromosomal representation (KQ983257.1) and (2) a NOVEL patch representing a variant of the region (KQ983258.1). A third haplotype of DUX4 region which is represented in GRCh37 will be also described.The DUX4 region contains tandem arrays of a 3.3 Kb D4Z4 macrosatellite repeat located in the sub-telomeric region of chromosome 4q. The number of D4Z4 repeats is highly polymorphic, ranging from 8 to 100 copies in the healthy individuals, but only 1 to 10 units in individuals with Facioscapulohumeral muscular dystrophy-1 (FSHD1: MIM#158900). The contraction of the repeat arrays is believed to result in a decreased epigenetic repression effect of D4Z4 and subsequent transcriptional activation of the DUX4 gene. Three main haplotypes, known as 4qA, 4qB and 4qA-L, have been reported for this region (1-3). The 4qB haplotype has homology to 4qA in the D4Z4 repeats, but is completely different in the distal region (1,2). 4qA, considered the reference haplotype, is the ancestral and most common haplotype. 4qA and 4qA-L are associated with FSHD, while 4qB is not (2). The different haplotypes exhibit population stratification (3).The GRC received user feedback that...
Source: GenomeRef - Category: Genetics & Stem Cells Source Type: blogs